This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Avastin (Bevacizumab) Plus Taxane-Based Therapy in Patients With Locally Recurrent or Metastatic Breast Cancer. (NCT00448591), a na phase 3 study. The primary outcome is Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00448591 |
| Phase | Phase 3 |
| Condition | Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2296 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
The study asked about the safety and effect on disease progression and overall survival of bevacizumab (Avastin) plus taxane-based chemotherapy in people with locally recurrent or metastatic breast cancer. The registry describes first-line treatment and a single-group study, so the central question is how outcomes were recorded among people receiving the regimen, not how it compared with a concurrently randomized control group.
Population
Patients with locally recurrent or metastatic breast cancer. The registry lists an enrollment of 2296 and identifies the primary outcome population as the Safety Population; details on how that population was defined are not reported in the registry record.
Intervention
Bevacizumab plus taxane-based chemotherapy. The summary describes bevacizumab at 10mg/kg intravenously every 2 weeks or 15 mg/kg intravenously every 3 weeks. Additional chemotherapy could be used, and alternatives were described for patients in whom taxanes were contraindicated.
Comparator
There was no separate comparator group in the registry design: the study is listed as single-group, with allocation recorded as NA and masking as none. Outcomes therefore describe participants receiving the regimen rather than a randomized treatment contrast.
Primary question
The primary outcome concerned the percentage of participants with adverse events and serious adverse events related to bevacizumab, death, and adverse events of special interest. The registry also lists disease progression and overall survival among secondary outcomes, but numerical results for those outcomes are not reported in the registry record.
This distinction matters when interpreting efficacy language. Without a concurrent randomized comparison, changes over time or observed outcomes cannot by themselves isolate the regimen’s effect from other influences. The registry record is most informative about the study’s safety outcome definitions and the event counts it posts.
3. Trial Design
The registry describes a Phase 3, open-label, single-group study sponsored by Hoffmann-La Roche. The listed condition is breast cancer, and the study title specifies locally recurrent or metastatic disease. The record gives a start date of 2006-09, a primary completion date of 2013-02, and a status of completed. Enrollment is listed as 2296.
All participants were to receive bevacizumab with taxane-based chemotherapy. The summary specifies bevacizumab at 10mg/kg intravenously every 2 weeks or 15 mg/kg intravenously every 3 weeks. The regimen could include additional chemotherapy. If taxanes were contraindicated, the summary allowed alternative chemotherapy other than anthracyclines or pegylated liposomal doxorubicin. Anticipated time on study treatment was until disease progression. The summary describes a target sample size of 500+ individuals; the relationship between that target and the enrollment entry is not explained in the registry record.
Because there is a single group and no masking, the design is not a randomized, blinded comparison. The registry lists allocation as NA and masking as none; a separate control arm is not described. This design can record events and outcomes observed during treatment, but does not supply a randomized estimate of how outcomes would differ under another treatment.
The primary outcome timeframe began on Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and extended up to 6 months after the last bevacizumab infusion. Investigators assessed adverse events, including laboratory abnormalities, according to National Cancer Institute - Common Toxicity Criteria grading systems. Details such as visit windows, rules for treatment discontinuation, and how missing assessments were handled are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Bevacizumab |
|---|---|
| STARTED | 2296 |
| COMPLETED | 0 |
| NOT COMPLETED | 2296 |
Reasons for not completing this period:
| Reason | Bevacizumab |
|---|---|
| Withdrawal by Subject | 178 |
| Progressive Disease | 1382 |
| Adverse Event | 382 |
| Protocol Violation | 41 |
| Lost to Follow-up | 19 |
| Treatment Regimen Completed | 70 |
| Other | 154 |
| Termination of Study | 70 |
Analysis population for the primary outcome, as defined in the registry: Safety Population
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: The safety/intent-to-treat (ITT) population was defined as all participants who had signed informed consent, with at least one valid post-baseline assessment and who received at least one dose of bevacizumab.
| Characteristic | Unit | Bevacizumab |
|---|---|---|
| Participants analysed | 2264 | |
| Age, Continuous | years | 53.2 (SD 11.0) |
| Sex: Female, Male: Female | Participants | 2252 |
| Sex: Female, Male: Male | Participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs), measured over Day 1 of Cycles 1, 2, 3, 4, 5, and 6 up to 6 months after the last bevacizumab infusion.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with adverse events and serious adverse events related to bevacizumab, death, and adverse events of special interest. The registry describes assessment of adverse events, including laboratory abnormalities, by the investigator using National Cancer Institute - Common Toxicity Criteria grading systems. The recorded timeframe starts on Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and extends up to 6 months after the last bevacizumab infusion.
A percentage endpoint expresses how common a recorded event was within a defined population during a specified observation period. Safety endpoints are used to characterize the types and frequency of events observed while participants receive treatment. The seriousness category distinguishes events classified as serious from other adverse events; the posted record also identifies selected serious adverse-event terms. These summaries describe events in the study population and do not, on their own, establish that treatment caused each event.
The endpoint title includes death and adverse events of special interest, but the registry record does not provide a complete numerical result for each named category. The serious and other adverse-event counts are listed for the bevacizumab group, while a death count is not reported. The detailed criteria for adverse events of special interest are not reported in the registry record. Thus, the stated endpoint defines the safety question, but the available entries do not fully document every component of its result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study is a single-group safety and outcome record, not a randomized comparison. Its design means the posted adverse-event counts describe people in the bevacizumab group; they do not estimate an event-rate difference against an untreated group or another regimen. The registry lists 2296 as enrollment, while the adverse-event entry uses 2264 as the at-risk count. Why these counts differ is not reported in the registry record, and no reason should be inferred from the entries alone.
For serious adverse events, the record lists 672 affected among 2264 at risk in the bevacizumab group. For other adverse events, it lists 2095 affected among 2264 at risk. These are recorded counts, not a causal comparison. The record also lists serious adverse-event terms with percentages: febrile neutropenia, 5.2%; neutropenia, 4.3%; pyrexia, 1.1%; dyspnoea, 1.0%; pulmonary embolism, 0.9%; and vomiting, 0.9%. The entries do not provide confidence intervals for these terms or explain whether the terms overlap within participants.
Precision cannot be fully assessed from counts alone. A confidence interval would communicate the range of values compatible with the observed data under a statistical model, but no interval estimates are reported in the registry record. No p-values or other inferential analyses are listed. The registry also does not report adjusted estimates or a method for handling repeated events, so the event counts should not be treated as adjusted treatment effects.
The record lists disease progression, time to progression, recorded death, overall survival, and best overall response as secondary outcomes. Numerical results for these outcomes are not reported in the registry record. Therefore, the title and study purpose signal interest in progression and survival, but the available results do not quantify those outcomes or establish a treatment effect on them.
The status is completed, but completion does not by itself indicate that every planned result is available in the registry. The record lists six outcome measures and no analyses. This absence limits interpretation: readers cannot evaluate outcome-specific estimates, uncertainty, or the extent to which analyses followed a prespecified plan. The registry record also does not report a comparator, so observed outcomes cannot be attributed to bevacizumab plus chemotherapy by contrasting them with another treatment group.
9. Statistical Methods Explained
Statistical interpretation starts with the study design. In a randomized comparative trial, assignment to treatment groups can support an estimate of the contrast between treatments, subject to the trial’s conduct and analysis. In this record, the design is single-group, allocation is listed as NA, and masking is none. The posted outcomes therefore describe the observed group. They do not estimate a randomized between-group effect.
What does a percentage endpoint represent?
Generally, a percentage endpoint divides the number of participants meeting an event definition by the relevant population at risk, then expresses that proportion on a percentage scale. It is important to know both the numerator and denominator and to know which participants were eligible for the calculation. The registry labels the primary outcome as a percentage of participants and identifies the Safety Population. The posted adverse-event entries give affected counts and at-risk counts, but details about the population definition and any exclusions are not reported in the registry record.
A participant-based percentage is different from an event count that can include multiple events for the same participant. The record labels the displayed entries as affected participants, but does not describe event recurrence, episode counting, or whether one person could contribute to several listed terms. Consequently, the counts should be read as the posted participant-level summaries, not as a complete account of the total number of event episodes.
Why distinguish serious from other adverse events?
Generally, seriousness and severity are separate concepts. Seriousness classifies an event according to regulatory or clinical criteria, while severity describes its intensity or grade. The record reports assessment using National Cancer Institute - Common Toxicity Criteria grading systems, but further details on the specific grading version and event-level rules are not reported in the registry record. The serious adverse-event count and other adverse-event count should therefore be understood as separately labeled summaries, not as interchangeable measures.
How should uncertainty be assessed?
Generally, a confidence interval communicates statistical uncertainty around an estimate. It is not a guarantee that the true value lies within the interval; rather, it is interpreted under the assumptions of the method used. The registry record does not report confidence intervals for the primary safety outcome or the listed serious adverse-event terms. It also does not provide inferential tests for these entries. The reported counts and percentages can be described, but their precision cannot be fully evaluated from the record.
Over-dispersion is a general concern when observed variability is greater than a model assumes. For event data, repeated events, clustering, or differences in follow-up can make simple models understate uncertainty if those features are not addressed. The registry record does not report a model for recurrent events or a procedure for accounting for variation in follow-up. No conclusion about whether over-dispersion was present or handled can be drawn.
What do the planning illustrations mean?
Generally, sample-size planning asks how many participants may be needed to detect a specified effect under chosen assumptions. The planning illustration associated with the posted results is explicitly not the trial’s own design calculation. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its assumed effect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is based on a total number of events, while other outcomes use participants per arm.
Those assumptions do not turn this single-group study into a two-arm randomized trial. Any such sample-size values are planning illustrations, not observed power and not evidence that the study was designed or analyzed according to those assumptions. The registry record does not report the trial’s own sample-size justification, a target effect used in its design, or a statistical analysis plan. It also does not report an interim-analysis plan.
What can the secondary outcomes add?
Progression and survival outcomes generally require clear event definitions, follow-up rules, and methods for handling participants whose event status is not known through the end of observation. Time-to-event methods can account for differing follow-up durations when their assumptions and censoring rules are appropriate. The registry lists time to progression and overall survival, but numerical results and the corresponding analysis methods are not reported in the registry record. Those methods cannot be inferred from the outcome names alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and secondary outcomes covering disease progression, time to progression, recorded death, overall survival, and best overall response. The record includes six outcome measures, but does not report a multiplicity strategy. When a study examines several outcomes, multiplicity can increase the chance that at least one result appears notable by chance. Statistical plans may address this through prespecified hierarchies or adjustments, but no such approach is reported in the registry record.
Missing-data handling is also not reported in the registry record. The record does not explain how participants with incomplete safety follow-up, missing assessments, or unavailable progression or survival status were treated. It does not provide the number of participants contributing to each secondary outcome or describe censoring rules. Without those details, the extent and potential impact of missing outcome information cannot be assessed.
The primary outcome identifies the Safety Population, but its membership criteria are not reported in the registry record. The adverse-event entries use 2264 as the at-risk count, while enrollment is listed as 2296; the reason for the difference is not reported. The record also does not describe whether the analysis included all enrolled participants, only those who received treatment, or a separately defined safety set beyond naming the Safety Population.
No analyses are listed in the registry record. As a result, there are no reported analysis populations, adjusted estimates, confidence intervals, or p-values to evaluate for the listed outcomes. The absence of these details does not establish that analyses were not conducted outside the registry; it means their methods and results are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bevacizumab | 672 | 2264 | 29.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bevacizumab | 2095 of 2264 |
Most frequent serious adverse event terms
| Event term | Organ system | Bevacizumab |
|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 117 of 2264 |
| Neutropenia | Blood and lymphatic system disorders | 98 of 2264 |
| Pyrexia | General disorders | 26 of 2264 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 23 of 2264 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 21 of 2264 |
| Vomiting | Gastrointestinal disorders | 20 of 2264 |
| Pneumonia | Infections and infestations | 17 of 2264 |
| Sepsis | Infections and infestations | 17 of 2264 |
| Device related infection | Infections and infestations | 16 of 2264 |
| Hypertension | Vascular disorders | 16 of 2264 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bevacizumab |
|---|---|---|
| Fatigue | General disorders | 1111 of 2264 |
| Alopecia | Skin and subcutaneous tissue disorders | 934 of 2264 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 867 of 2264 |
| Hypertension | Vascular disorders | 760 of 2264 |
| Nausea | Gastrointestinal disorders | 667 of 2264 |
| Stomatitis | Gastrointestinal disorders | 657 of 2264 |
| Proteinuria | Renal and urinary disorders | 618 of 2264 |
| Diarrhoea | Gastrointestinal disorders | 613 of 2264 |
| Neutrophil count decreased | Investigations | 587 of 2264 |
| White blood cell count decreased | Investigations | 566 of 2264 |
Serious events with the highest arm-level rate: febrile neutropenia (5.2%), neutropenia (4.3%), pyrexia (1.1%), dyspnoea (1.0%), pulmonary embolism (0.9%).
The registry lists 672 affected participants among 2264 at risk for serious adverse events in the bevacizumab group. For other adverse events, it lists 2095 affected among the same at-risk count. These are distinct registry categories; the record does not explain whether participants could appear in both summaries, and the counts should not be added together.
The listed serious adverse-event terms and percentages are febrile neutropenia, 5.2%; neutropenia, 4.3%; pyrexia, 1.1%; dyspnoea, 1.0%; pulmonary embolism, 0.9%; and vomiting, 0.9%. These entries identify selected terms, not necessarily every serious adverse event recorded. The registry record does not report confidence intervals for the percentages, explain whether participants could have more than one term, or state how the listed terms were selected.
The primary outcome title also mentions death and adverse events of special interest. A death count is not reported in the adverse-event entry, and definitions or full results for adverse events of special interest are not reported in the registry record. The reported safety summaries describe events observed in the study group; in a single-group study, they do not by themselves establish that treatment caused an event or quantify risk relative to another regimen.
12. What the Result Does, and Does Not, Mean
The posted results describe safety-event counts in a single-group study of bevacizumab plus taxane-based chemotherapy. The registry lists 672 participants affected by serious adverse events and 2095 affected by other adverse events, each against an at-risk count of 2264. It also posts selected serious adverse-event terms and percentages. These are descriptive summaries of recorded events in the bevacizumab group.
The figures do not provide a randomized comparison. Without a concurrent control group, the record cannot show how the observed event burden differs from what would have occurred under another treatment. Nor do the counts alone establish that bevacizumab, chemotherapy, the underlying cancer, or another factor caused a particular event. The listed percentages describe observed terms; they do not provide a causal estimate.
The registry’s study purpose includes disease progression and overall survival, and its secondary outcomes include time to progression and best overall response. However, numerical results for those outcomes are not reported in the registry record. The available entries therefore do not quantify progression, survival, or response, and do not establish an effect on those outcomes. A completed status does not substitute for outcome results or an analysis plan.
The primary endpoint includes death and adverse events of special interest, but the corresponding complete numerical results are not reported. Confidence intervals, p-values, and details about missing data are also not reported in the registry record. These omissions limit assessment of uncertainty, completeness, and the robustness of interpretation.
In general, clinical decisions require evidence considered in context, including comparative evidence and the full clinical record. The registry information supports a limited statistical reading: it documents the study design and selected safety summaries, while leaving key efficacy estimates and analytical details unavailable. It does not support a claim that the regimen does or does not work.
13. Why This Trial Matters Statistically
This trial is statistically notable because its broad clinical question includes safety, disease progression, and overall survival, while its listed design is single-group and open-label. The distinction between a treatment cohort and a randomized comparison is central: descriptive outcomes can characterize what was recorded during treatment, but they cannot isolate the effect of treatment from other explanations.
The record also illustrates why endpoint definitions and analysis populations matter. The primary outcome is described as a percentage of participants, and the safety population is named, but the population rules and missing-data procedures are not reported. The registry lists enrollment as 2296 and uses 2264 as the at-risk count for the adverse-event summaries. Without an explanation of that difference, readers cannot determine from the record which participants contributed to the safety counts or why.
Safety interpretation also depends on the distinction between serious adverse events and other adverse events, and on understanding how event terms are counted. The record gives selected percentages for serious adverse-event terms but does not report uncertainty intervals or whether a participant could contribute to multiple terms. Such details affect how precisely and completely those summaries can be interpreted.
Finally, the record lists progression and survival outcomes without numerical results or analyses. That gap separates the stated clinical aims from the results available for statistical assessment. The planning illustration assumptions do not fill it: planning values are not observed power, and their two-arm assumptions are not the design of this single-group study. These features make clear why design, outcome reporting, analysis methods, and uncertainty should be considered together.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
A key limitation is the absence of a separate comparator group. The study is listed as single-group, with allocation recorded as NA and masking as none. Consequently, the posted data do not support a randomized treatment contrast, and observed events cannot be interpreted as effects relative to another regimen.
The registry record does not report numerical results for the listed secondary outcomes of disease progression, time to progression, recorded death, overall survival, and best overall response. It also does not report confidence intervals, p-values, or an analysis plan. The record therefore provides limited information for assessing the magnitude and precision of outcomes beyond the posted adverse-event summaries.
The adverse-event entry lists 2264 at risk, while enrollment is 2296; the reason for this difference is not reported in the registry record. The Safety Population is named, but its eligibility rules and relationship to the enrollment entry are not described. The death count, definitions of adverse events of special interest, and handling of missing safety assessments are also not reported.
Only selected serious adverse-event terms are listed. The registry record does not explain how those terms were selected, whether a participant could contribute to multiple terms, or provide uncertainty estimates for the listed percentages. Follow-up details beyond the stated primary outcome timeframe, treatment exposure summaries, and rules for discontinuation are not reported. These omissions constrain evaluation of the completeness and precision of the safety findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Avastin (Bevacizumab) Plus Taxane-Based Therapy in Patients With Locally Recurrent or Metastatic Breast Cancer. — NCT00448591.
- Registry record last updated 2015-05-25; status last verified 2015-05.
- Results first posted 2015-05-25.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed Phase 3, open-label, single-group study of bevacizumab plus taxane-based chemotherapy in patients with locally recurrent or metastatic breast cancer. It lists Hoffmann-La Roche as sponsor, enrollment of 2296, a start date of 2006-09, and primary completion in 2013-02. The primary outcome concerns adverse events and serious adverse events related to bevacizumab, death, and adverse events of special interest.
The safety entry lists 672 affected among 2264 at risk for serious adverse events and 2095 affected among 2264 at risk for other adverse events. Selected serious adverse-event terms are reported as percentages. Numerical results for the listed progression and survival outcomes, analysis methods, uncertainty estimates, and explanations for missing or differing counts are not reported in the registry record. The single-group design supports descriptive interpretation of recorded outcomes, not a randomized comparison.